Long-Term Risks of Vasectomy

Because vasectomies are usually performed on men who are in their thirties and forties at the time of the procedure, several decades of life remain after vasectomy during which long-term effects on health might manifest themselves. Because large numbers of men are exposed to such a risk for a long period of time, an adverse effect of vasectomy on health could have far-reaching negative consequences for public as well as individual health.

Concern about the possibility of long-term risks of vasectomy was fueled by findings that vasectomy may accelerate development of atherosclerosis in monkeys,^{1, 2} but it originated in observations that a high proportion of men with vasectomy develop anti-sperm antibodies.^{3, 4, 5, 6, 7, 8, 9, 10} Results of studies conducted over nearly four decades, however, provide little evidence of any significant long-term side effects of vasectomy. Current guidelines from the American Urological Association¹¹ and the European Association of Urology¹² reflect this in their recommendation for preoperative counselling for men/couples considering vasectomy (see Box 1). Nonetheless, the topic remains of considerable interest with reports of studies on the topic appearing regularly in the scientific literature.

Box 1 Vasectomy counselling recommendations related to long-term risks following vasectomy^{11, 12}







 

After vasectomy, male sexual and reproductive physiology remains unaffected, aside from the desired change in fertility. The nerves involved in erectile function and ejaculation are not affected, and vasectomy does not lead to impotence or other sexual difficulties.^{13, 14, 15} In a large cohort study,^{16, 17} incidence of impotence was 1.9/1000 man-years (MY) of observation in men with vasectomy and 1.7/1000 MY in men without vasectomy, a difference that was not statistically significant.

As with female sterilization, vasectomy has sometimes been reported to have a positive effect on sexuality, possibly because the chance of unintended pregnancy has been reduced.^{18, 19, 20, 13, 14, 15} In one large study, the number of men reporting loss of sexual interest was identical in vasectomized versus nonvasectomized men.²¹

Production of seminal fluid, the major component of semen, by the accessory sex glands is unaffected by vasectomy. Thus, the client will not notice any reduction in the amount of semen ejaculated after vasectomy has been performed. Sperm production continues, even though the sperm's passage through the reproductive tract has been blocked; sperm are broken down by macrophages in the lumen of the epididymal tubule.^{4, 22} Sometimes the blockage in the reproductive tract after vasectomy causes pressure to build up in the epididymis, which leads to distension in the tubules and, in time, rupture. Ruptures are usually asymptomatic and not problematic. Sperm granulomas that can form at the site of the rupture do not usually require treatment. Some vasectomy providers believe that this buildup can be avoided by leaving open the testicular end of the vas.

Although some early prospective studies suggested that mean plasma levels of testosterone, luteinizing hormone (LH), and estradiol increased after vasectomy when compared with mean hormone levels measured before vasectomy, the changes were found to be within the normal range for adults.²³ Studies in animals suggesting an effect of vasectomy on testicular weight and Leydig cell morphology, which were never confirmed,^{24, 25, 26} generated sufficient concern that a large number of studies regarding endocrine function in man have been done. The results of these studies are summarized in Table 1.

Table 1. Studies of the effects of vasectomy on testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH)

*In men >20 years postvasectomy, testosterone levels were significantly higher than in age-matched controls.
0, no significant change; + , statistically significant increase; NM, not measured

In nearly all longitudinal studies and all of the cross-sectional studies (with the exception of that of Mo and colleagues,⁴⁸ who reported significantly higher testosterone levels in men >20 years postvasectomy compared with age-matched controls), no significant association of vasectomy with changes in the concentrations of testosterone, LH, or follicle-stimulating hormone (FSH) was found. Thus, despite isolated findings of a significant association of vasectomy with changes in some hormones, the bulk of the extensive research on the subject provides strong evidence that vasectomy has no effect on testosterone or the pituitary gonadotropins at least up to 25 years after the operation.

Histological and morphometric examination of seminiferous tubules and testes of vasectomized men showed that some of the normal ultrastructure was maintained.^{50, 51, 52, 53} For example:

• the blood supply to the tubules was intact
• seminiferous tubules were normal in terms of patency, diameter and basement membrane
• Sertoli cells appeared to be intact and
• the normal stages of spermatogenesis were evident.

Histological abnormalities noted, however, included sperm abutting the basal portion of the Sertoli cells, instead of being observed in their typical location close to the lumen,⁵⁰ increased thickness of the seminiferous tubular walls,^{26, 54, 55, 56} reduced number of spermatids,^{54, 56, 57} increased focal interstitial fibrosis,^{26, 52, 54, 55, 56} and decreased numbers of sperm/gram of testis.⁵⁶

How these changes occur and their significance remain unclear.

Some men with these changes have been able to produce offspring following vasectomy reversal^{58, 54, 59} or assisted reproduction.⁵⁶ In one study in which fertility was examined in relation to histologic changes, interstitial fibrosis was significantly correlated with infertility in men who had a successful vasectomy reversal determined by sperm in the ejaculate, but none of the other vasectomy-associated histologic abnormalities were associated with infertility after vasectomy reversal.⁵⁴ Long-term spermatogenic damage has not been seen in men up to 39 years after vasectomy and there is no increase in sperm aneuploidy (an abnormal number of chromosomes) following vasectomy.50^{, 52, 53}

.

Although numerous studies have examined the effects of vasectomy on the epididymis in various laboratory animals, similar studies in men are lacking.⁶⁰ The mechanism whereby sperm can be accommodated in the human epididymis following vasectomy is still not known, but at least clinicopathologically, it does not resemble the events that occur in the rabbit, rat, and hamster, where despite species' variation in the ability of the proximal vas and epididymis to distend following vasectomy, the epididymis may ultimately rupture.⁶⁰

Epididymitis (inflammation of the epididymis often accompanied by swelling and pain) in vasectomized men has been referred to as 'congestive' epididymitis. It is rarely of infectious origin, instead it is caused by distension of the epididymis owing to continued passage of sperm from the testis into the epididymis with no outflow given the occluded vas.^{61, 62, 63} Epididymitis following vasectomy is uncommon, with most studies reporting rates of approximately 1–3% of men who have had a vasectomy, but rarely have unvasectomized controls been included in these studies.¹¹

Some degree of epididymal dilatation or distension has been reported in 70–100% of the men undergoing vasectomy reversal, but most men do not have any symptoms.^{64, 65, 66} Ultrasound studies have found that epididymal enlargement is common and may not be associated with any pain or discomfort.^{67, 68} On ultrasound examination, vasectomized men had a significantly higher incidence of thickened epididymides, epididymal tubular ectasia (when the normally invisible epididymal tubules are visible), sperm granulomas and mobile echogenicities (thought to be clumps of sperm trapped within dilated epididymal tubules) compared to non-vasectomized controls.^{69, 70} Histological changes have also been noted.^{71, 72, 73, 74} It is unclear if these changes are clinically significant.⁶⁹

The epididymis plays a critical role in sperm maturation; it is during transit through the epididymis that sperm gain their full fertilizing potential.⁷⁵ Vasectomy has been shown to affect gene expression and the synthesis of various proteins in the human epididymis, alterations that in some cases appear irreversible following vasovasestomy (i.e. reanastomosis of the cut ends of the vas).^{73, 76, 77} Some of these proteins may play a critical role in sperm maturation and may be responsible, at least in part, for the fact that pregnancy rates following vasovasestomy are consistently lower than rates of appearance of sperm in the ejaculate after vasectomy reversal (see Vasectomy Reversal chapter).

Thakur and colleagues studied maltase activity in semen, which reflects the secretory activity of the prostate, in 35 men vasectomized for 1–2 years and a comparison group of 24 nonvasectomized men.⁷⁸ They found that maltase activity in the semen of vasectomized men was significantly lower than in nonvasectomized men, and concluded that prostatic function was diminished by vasectomy. These findings were confirmed by Naik and associates who demonstrated that, in 78 men vasectomized for 1–8 years, seminal concentrations of maltase, in addition to prolactin, zinc, and magnesium, were significantly lower than in 22 nonvasectomized men of normal fertility.⁷⁹

However, total prostatic volume and growth rate do not appear to be affected by vasectomy.⁸⁰ Postvasectomy prostate-specific antigen levels have been significantly lower than preoperative levels for up to 6 months after vasectomy.⁸¹

The implications of these findings on changes in the secretory function of the prostate after vasectomy remain unknown. Further epidemiologic research on noncancerous prostatic disease in vasectomized men, in particular the relationship of the changes noted already to benign prostatic hypertrophy, would be of interest.

Human immunodeficiency virus (HIV) can be found in semen as free-floating virus, HIV infected seminal white blood cells (WBCs), and in association with sperm, with all three potentially playing an important role in the sexual transmission of HIV.^{82, 83, 84, 85, 86, 87, 88, 89} 

Preliminary data from Anderson and coworkers indicated that infectious HIV could be found in semen from some HIV seropositive vasectomized men.⁹⁰ Subsequently, 46 HIV-seropositive men were studied before vasectomy and for 3 months afterward; although levels of cell-free virus in the semen remained stable after vasectomy, cell-associated HIV was detected in significantly more men after vasectomy.⁹¹ Additionally, although the exact origin of the cell-free HIV and HIV infected WBCs in semen is unclear, it appears that HIV in the ejaculate arises from prostatic and seminal vesicle secretions, as well as the urethra.^{89, 92} Taken together, these results provide good evidence that vasectomy provides no protection against HIV transmission. This underscores the importance of counselling vasectomized men that vasectomy does not provide any protection against transmission or acquisition of HIV and other sexually transmitted infections (STIs) and that men need to use condoms consistently and correctly if they are at risk of transmitting or acquiring HIV/STIs.

Four large-scale, retrospective cohort studies have examined comprehensively the incidence of a number of diseases in vasectomized men and a comparison group of nonvasectomized men.^{93, 94, 95, 96, 97} In each, investigators identified retrospectively a group of men who were known to have had vasectomies and a comparison group of men not known to have had a vasectomy. The occurrence of hospitalizations after identification for the study was determined by computer-record linkage. The comparison groups were men hospitalized in the same years for an operation other than vasectomy;^{93, 94} men with the same prepaid medical care program;⁹⁵ men having routine health checkups who did not indicate on questionnaires that they had had a vasectomy previously;⁹⁶ and men admitted to the hospital for elective operations, appendicitis, or injury.⁹⁷ The designs of these four studies are summarized in Table 2, and the results of their comparison of disease incidence in vasectomized and nonvasectomized men are summarized in Table 3 and Table 4.

Table 2. Summary of designs of four record-linkage studies of disease incidence in vasectomized men and comparison subjects

Table 3. Summary of results of three record-linkage studies of disease incidence in vasectomized men and comparison subject. Adapted from references ^{93, 94, 95, 96}

*Scottish,^{93, 94} Puget Sound,⁹⁵ Kaiser⁹⁶

**Where given
†Ratio of standardized first-event rate in vasectomized men to average of standardized first-event rates in the three comparison groups

Table 4. Summary of results of disease incidence in vasectomized men and comparison subjects from the Oxford Record Linkage Study. Adapted from Nienhuis et al. Incidence of disease after vasectomy: A record linkage retrospective cohort study. BMJ 304;743, 1992⁹⁷

*Relative risk in men with a vasectomy compared with combined controls.

Of greatest importance, in all four studies, vasectomy was not significantly associated with increased risk of hospitalization for most disease categories. The total number of cases of disease in men in these studies is large for all categories, and taken together, the studies are reassuring that vasectomy does not increase the risk of adverse health outcomes.

In the study by Walker and associates,⁹⁵ vasectomy was associated with a significantly higher risk of diseases of the genitourinary system, including orchitis and epididymitis. A similar increased risk of orchitis/epididymitis was also seen in another large study.⁹⁸ The increase in risk was confined to the first years after vasectomy, and the authors attributed the findings to the occurrence of minor complications of vasectomy^{95, 98} and to the possibility that men who had recently undergone vasectomy might be more likely to seek medical attention for nonvasectomy-related genitourinary conditions.⁹⁵

In three of the studies,^{93, 94, 95, 96} the risk of hospitalization for mental disorders was lower in vasectomized men than in the comparison group. The most likely explanation is that men who elect to have a vasectomy are mentally more stable, because a causal relationship of vasectomy to better mental health is unlikely.

Walker⁹⁵ and Petitti ⁹⁶ and respective coworkers studied the risk of hospitalization separately in men with vasectomies of long duration—9 or more years in the Walker study and 10 or more years in the Petitti study. In both, there was no significant association of vasectomy of long duration with an increased risk of hospitalization for any of the categories of disease shown in Table 3.

Massey and colleagues reported the results of a fifth large retrospective cohort study, which examined the incidence of 98 diseases or conditions in 10,590 paired vasectomized men and neighborhood controls matched for age, race, and marital status.¹⁶ Additional data on this cohort were later reported by Schuman and associates.¹⁷ Of particular interest to those authors were diseases or conditions that could have been the immunopathologic consequences of anti-sperm antibodies. The median time of follow-up postvasectomy was over 8 years, ranging from 1 to 41 years. With the exception of epididymitis/orchitis, the occurrence of all other diseases examined was similar or lower in vasectomized men compared with controls. This included diseases or conditions in which a vasectomy-related immunopathologic mechanism may have played a role. The number of cases of epididymitis/orchitis was relatively low (33 per 10,000 MY in vasectomized men), and the major difference in occurrence between the vasectomized men and controls was during the first 12 months after vasectomy.

Petitti and colleagues²¹ also did a cross-sectional analysis in which they examined the prevalence of a large number of diseases and the existence of current symptoms of illness in 4385 vasectomized and 13,155 nonvasectomized men enrolled in the Kaiser-Permanente Medical Care Plan in the US. Of 45 diseases and symptoms that were examined, vasectomy was significantly, independently associated with joint pain or swelling, back trouble, and a history of kidney or bladder infection. The latter finding is consistent with the findings of Walker and associates:⁹⁵ that is, a higher risk of diseases of the genitourinary system in vasectomized men, although details on whether risk of kidney or bladder infection was elevated are not provided by Walker's group. No other studies have examined specifically the possibility of an association of vasectomy with joint pain or swelling and back trouble, although the occurrence of arthritis²¹ or the risk of hospitalization for arthritis^{16, 17, 95, 97} have not been shown to be higher in vasectomized than in nonvasectomized men.

Intense research efforts examining the association between vasectomy and cardiovascular disease in men were touched off by studies reporting that vasectomized monkeys had atherosclerosis of greater extent and severity than nonvasectomized monkeys.^{1, 2} It was postulated that vasectomy could increase the risk of atherosclerosis if anti-sperm antibodies that form as a consequence of vasectomy resulted in the production of circulating immune complexes that injure the vascular wall. Concern about the possibility that vasectomy might increase the risk of atherosclerotic cardiovascular disease in men has waned since publication of a large number of studies showing no association of vasectomy with various disease endpoints in men. In addition, two experimental studies, which attempted to replicate the original studies that showed an effect of vasectomy on atherosclerosis in monkeys, included larger numbers of monkeys and found no adverse effect of vasectomy on atherosclerosis.^{99, 100}

Since the early 1980s, numerous cohort, case–control, and cross-sectional studies have been conducted to examine potential associations between vasectomy and various cardiovascular disease endpoints, including acute myocardial infarction, other ischemic heart disease, stroke, nonsyphilitic aortic aneurysm, peripheral vascular disease, hypertension, coronary artery disease, and hypertensive and atherosclerotic retinal vascular changes. Table 5 provides a summary of studies on vasectomy and cardiovascular disease. These epidemiologic studies of cardiovascular disease in vasectomized men have, with few exceptions, shown no association of vasectomy with any manifestation of atherosclerosis or cardiovascular disease. Even in men with vasectomies of long duration (20 years or longer), no association of vasectomy with an increased risk of cardiovascular disease has been found.^{96, 101, 102, 103, 104} Taken together, the experimental studies in monkeys^{99, 100} and accumulated epidemiologic studies in men provide strong reassurance that vasectomy has no adverse effect on the cardiovascular system nor does it increase the risk of atherosclerosis in man.

Table 5. Summary of studies of vasectomy and cardiovascular disease

*All men in study had some degree of coronary artery disease
†Number of pairs in which a case occurred in one or both members
NR = not reported

In the late 1960s and the early 1970s, Roberts^{115, 116} suggested that the risk of thrombophlebitis might be increased following vasectomy. Results of a large-scale epidemiologic study, however, did not find increased risk of thrombophlebitis in vasectomized men.^{16, 17} In a prospective study, various measures of blood coagulation function were examined in 38 men before vasectomy and for 12 months following vasectomy and at the same timepoints in an age-matched, nonvasectomized comparison group.¹¹⁷ No differences were found between the vasectomized and the nonvasectomized men in any measures examined including prothrombin time, partial thromboplastin time, spontaneous platelet aggregation, circulating platelet aggregation ratios, or levels of fibrinogen, Factor V, Factor VII, fibrin monomer, and fibrin digestion products.

Petitti and coworkers¹¹⁸ used information from comprehensive multiphasic health checkups in 4385 vasectomized and 13,155 age- and race-matched, nonvasectomized men to study the association of vasectomy with a large number of physiologic measures. In this group, vasectomy was not significantly associated with alterations in any of the following: diastolic blood pressure, white blood cell count, hemoglobin, hematocrit, mean corpuscular hemoglobin, mean cell volume, mean corpuscular hemoglobin concentration, sodium, calcium, cholesterol, glucose, uric acid, blood urea nitrogen, creatine, total bilirubin, alkaline phosphatase, lactic dehydrogenase, and glutamic-oxaloacetic transaminase. The vasectomized men had a significantly higher mean serum potassium concentration (4.6 versus 4.5 mEq/L) and significantly lower systolic blood pressure (128.9 versus 130.4 mmHg) than nonvasectomized men. The overall differences in these measures, although statistically significant, were considered unlikely to be biologically important even if they were causally associated with vasectomy. In three additional studies that examined the effect of vasectomy on systolic and diastolic blood pressure, two found that the mean systolic and diastolic blood pressures were not significantly different between vasectomized and nonvasectomized men;^{107, 119} the other found that both were lower in vasectomized men than in nonvasectomized men.¹²⁰ Verheught and associates measured serum cholesterol before and 3 months after vasectomy in 24 men and in a control group of 23 men of similar age.¹²¹ No significant differences in cholesterol concentration were measurable between the two groups at baseline, nor was a significant change in cholesterol found after vasectomy.

Taken together, these studies indicate that vasectomy is not associated with changes in the physiologic functions measured by these tests.

An increased occurrence of circulating sperm-agglutinating antibodies in vasectomized men was first reported by Phadke and Padukone in 1964.⁴ Subsequently, numerous investigators have confirmed the presence of anti-sperm antibodies in association with vasectomy.^{5, 7, 8, 9, 10, 122, 123, 124}

The clinical significance of anti-sperm antibodies in men after vasectomy has been the subject of many investigations, and a number of potential mechanisms whereby they might lead to disease have been suggested, including:

• anti-sperm antibodies might trigger production of antibodies to other cells which might lead to disease
• sperm antigens may combine with the anti-sperm antibodies to produce circulating immune complexes that could cause tissue damage and inflammation¹
• vasectomized men may have immunity to tumor-associated antigens that could affect directly the development of tumors.¹²⁵
  

However, numerous studies conducted over the past few decades have shown no evidence of any immunologic or other diseases related to development of anti-sperm antibodies following vasectomy.^{6, 16, 95, 98, 103, 106, 126, 127} Anti-sperm antibodies may be associated with decreased fertility following vasectomy reversal (see chapter 'Reversing Vasectomy').

Anti-sperm antibodies

Because sperm first form at puberty, they are autoantigenic. Normally, sperm antigens are not exposed to the immune system because of the blood–testis barrier and other epithelial barriers along the reproductive tract. Development of anti-sperm antibodies after vasectomy is thought to be related to breakdown of the blood–testis barrier¹²⁸ and leakage of sperm antigens from the epididymis.¹²⁰ Sperm antigens have been found in the serum of men as early as 2 weeks after vasectomy.¹²⁹

Anti-sperm antibodies are found in between 8% and 21% of men in the general population and in 9% and 36% of infertility patients.¹²⁸ In contrast, circulating sperm agglutinating antibodies are found in 50–80% of men in the first year after vasectomy.^{4, 5, 6, 7, 8, 9, 10, 130} Approximately 3% of nonvasectomized men have sperm-immobilizing antibodies,¹²⁰ whereas anywhere from 25 to 60% of men develop sperm-immobilizing antibodies in the first year after vasectomy.^{7, 8, 9, 10} A small percentage of men who do not develop anti-sperm antibodies in the first year after vasectomy develop them in the second or third year after the procedure.^{6, 131}

Although serum anti-sperm antibodies are common following vasectomy, fewer men have these antibodies in their seminal plasma.¹³² Following surgery for vasectomy reversal, however, anti-sperm antibodies are more commonly found in seminal plasma¹²⁸ and are found on the surface of sperm as well.^{128, 133}

Antibodies to protamines, proteins found in the nucleus of the sperm, are detectable in between 20% and 40% of vasectomized men but are virtually undetectable in nonvasectomized men.^{122, 123, 124, 134} The presence of antiprotamine antibodies has been of special concern because of fear that vasectomy might lead to formation of anti-deoxyribonucleic acid (DNA) antibodies, because DNA is the other main constituent of the sperm nucleus. To date, however, anti-DNA antibodies have not been detected in vasectomized men.^{122, 124}

Large variations occur in the titers of both sperm-agglutinating and sperm-immobilizing antibodies in men following vasectomy.^{9, 120} Few studies have examined what happens to anti-sperm antibody titers over time. The results of those that have examined the issue are conflicting, with some investigators^{135, 136} reporting no change and others^{8, 120} reporting an increase over time.

Little is known about the factors that affect either the development of anti-sperm antibodies or the titer of the antibodies in the men who do develop them. Some evidence suggests that age at vasectomy plays a role, with younger men being more likely than those older to develop antisperm antibodies.^{120, 124} A family history of autoimmune disease is not associated with development of anti-sperm antibodies.¹²⁴

One small case–control study reported that vasectomy may be a risk factor for dementia (specifically primary progressive aphasia).¹³⁷ The authors suggested that this increased risk could be related to the presence of anti-sperm antibodies following vasectomy, with the anti-sperm antibodies somehow affecting the brain because sperm share antigenic epitopes with brain tissue. Unfortunately, anti-sperm antibody levels were not measured in that study population. Results of a subsequent small study found no association between anti-sperm antibodies and Alzheimer’s disease, another form of dementia.¹³⁸ Additionally, no increases in any mental disorders were reported in three large epidemiologic studies.^{93, 94, 95, 96} Selection bias, misclassification of data and confounding may have contributed to the reported relationship between anti-sperm antibodies and primary progressive aphasia.¹³⁹    

Other autoantibodies

If development of anti-sperm antibodies caused or was accompanied by the development of other antibodies, particularly other autoantibodies, a mechanism linking vasectomy with disease in men would be established, because many diseases in humans are associated with increases in autoantibody levels.

Several investigators have studied this possibility by examining the presence of various autoantibodies including rheumatoid factor and anti-thyroid, anti-nuclear, anti-mitochondrial, anti-parietal cell, anti-thyroglobulin, anti-liver, antikidney, and anti-smooth-muscle antibodies in men before and after vasectomy or in vasectomized compared with findings in nonvasectomized men.^{10, 123, 124, 140, 141, 142, 143, 144, 145} Results of these studies indicate that vasectomy is not associated with clinically significantly increased levels of autoantibodies other than anti-sperm antibodies.

Although two studies reported that vasectomized men developed cytotoxic antibodies,^{146, 147} results of larger, well-designed studies using before and after measures of cytotoxic antibodies were unable to demonstrate any change in the level of cytotoxic antibodies after vasectomy.^{10, 148, 149}

Finally, results of several large-scale epidemiologic studies have not shown an increased incidence or prevalence of autoimmune disease in vasectomized compared with findings in nonvasectomized men.^{16, 17, 93, 94, 95, 96, 97, 98}

Thus, taken together, these studies provide convincing evidence that vasectomy does not lead to development of autoantibodies in man other than anti-sperm antibodies.

Circulating immune complexes

Immune complexes form when an antibody combines with its antigen, and in some circumstances, immune complexes may be deposited in tissues such as the renal glomerulus, joints, and arterial walls, leading to inflammation and tissue necrosis. It has been suggested that continuous production of anti-sperm antibodies after vasectomy could lead to the formation of circulating immune complexes with subsequent development of various diseases. Some investigators have hypothesized or demonstrated this is to be the case in laboratory animals following vasectomy, including atherosclerosis in monkeys¹ and orchitis and glomerulonephritis in rabbits.¹⁵⁰

Studies to detect circulating immune complexes in vasectomized men have produced conflicting results. Several investigators have demonstrated the presence of circulating immune complexes in small percentages of men following vasectomy.^{140, 151, 152} One study demonstrated a higher incidence and higher levels of circulating immune complexes in men who were vasectomized for a mean of nearly 8 years compared with those in age-matched controls.¹⁵³ Numerous others, however, have reported no association of vasectomy with circulating immune complexes or have demonstrated only a transient increase in circulating immune complexes following vasectomy, which disappear by 3 months to 1 year after vasectomy.^{123, 124, 129, 145, 110} In the study with the longest follow-up after vasectomy, no differences were found in the level of circulating immune complexes in vasectomized men (mean time since vasectomy nearly 16 years) compared with those in nonvasectomized men.¹²⁰

Although the evidence indicates that at least in some men, and for some time, circulating immune complexes occur following vasectomy, they do not appear to be clinically relevant. Results of a number of large-scale epidemiologic studies have not shown increased incidence or prevalence of various diseases that could be related to immune complex deposition, including atherosclerosis and glomerulonephritis in vasectomized compared with nonvasectomized men.^{16, 17, 94, 96, 97, 111}

Globally, prostate cancer is the second most common cause of cancer in men.¹⁵⁴ In the United States it is the most commonly diagnosed cancer among men; twice as common in 2013 as the next leading cause (lung and bronchus cancer).¹⁵⁵ Little is known about the etiology and pathogenesis of prostate cancer, with the only well-defined risk factors being family history of prostate cancer,  increasing age, and black ethnicity.¹⁵⁶ Black men appear to be more susceptible to prostate cancer due to genetic factors, but data suggest that other factors such as diet and socioeconomic status also play a role, with incidence rates among black men varying from one country to another.¹⁵⁷

Almost 30 epidemiologic studies of vasectomy and the risk of prostate cancer have been reported in the literature since the mid-1980s (Table 6). Results of these studies have been difficult to interpret for several reasons: conflicting research findings have been reported; a convincing biologic mechanism for a causal relationship has been lacking; when associations have been found, they have been generally weak; and some studies have had the potential for bias (detection, misclassification, recall and/or confounding bias).

Table 6. Summary of studies of vasectomy and prostate cancer

*Number of years postvasectomy.
NR, not reported.

In 1990, there was a report of a case–control study showing a three- to sixfold increased risk of prostate cancer in vasectomized men.¹⁶¹ The methodology used in this study was to screen data gathered from hospital interviews to look for associations between risk factors and diseases. Associations identified in studies using this methodology often appear more highly significant than they actually are owing to the potential for various forms of bias.¹⁸² In a subsequent report of another case–control study by the same authors using additional data from the same surveillance system, a lower and nonsignificant association between vasectomy and prostate cancer was described.¹⁶⁷

There were four other case–control studies and one cohort study published in the late 1980s and early 1990s. Two of the five studies reported a moderate but significant elevated risk of prostate cancer in vasectomized men,^{160, 163} one reported a nonsignificant increased risk,¹⁵⁹ and the other two reported no increased risk.^{158, 183} Limitations, including detection and misclassification bias, were possible in all of these studies.¹⁸⁴

Two cohort studies published in 1993 by Giovannucci and coworkers reported weak positive associations between vasectomy and prostate cancer and relative risks that increased over time.^{164, 165} These studies provided the best evidence for a causal link between vasectomy and prostate cancer, and prompted the US National Institutes of Health (NIH) to convene a panel of experts to review the data available at that time. The panel concluded that the associations that had been reported to date were weak and that there was a strong potential for detection bias in the studies because much prostate cancer is undetected and underreported, and because vasectomized men may be more likely than other men to be screened for prostate cancer or seek health care services, leading to the appearance of an elevated risk of prostate cancer in vasectomized men.¹⁸⁵

Since that time, there have been 19 additional studies on vasectomy and prostate cancer published (Table 6). Sixteen showed no significant increased relative risk of prostate cancer in vasectomized men, confirming the probability that some of the earlier studies were subject to bias. Epidemiologic studies of relatively weak associations between a procedure such as vasectomy and a chronic disease such as prostate cancer are difficult because of the potential for bias.¹⁸⁶ Recently results of long-term (24 years) follow-up of the cohort first described by Giovannucci¹⁶⁴ in 1993 were published.¹⁸⁷ The authors reported that while vasectomy was not significantly associated with risk of low-grade prostate cancer, vasectomized men were at an increased risk of high-grade (Gleason score 8–10) and lethal prostate cancer (see Table 6).

Authors of two meta-analyses of published studies on vasectomy and prostate cancer concluded that numerous sources of bias may have led to an overestimation of any effect of vasectomy on prostate cancer.^{188, 189} More recently, as part of the process of updating their vasectomy guidelines, the American Urological Association (AUA) performed a meta-analysis of 10 comparative cohort studies and found that there was no statistically significant difference in relative risk of prostate cancer in vasectomized men compared to men without a vasectomy and no relationship between time since vasectomy or age at time of vasectomy and prostate cancer. (Sharlip et al 2010). None of these three meta-analyses included the recently published Siddiqui article (Siddiqui et al 2014),¹⁸⁷ although they did include the article describing the earlier findings from this cohort.¹⁶⁴ The analysis of the long-term follow-up has the same potential for confounding, information and selection bias that the original analysis had and the authors note that the relative risk of lethal prostate cancer translates into a small increase in absolute risk. (Siddiqui et al 2014).¹⁸⁷ 

Taken as a whole, these studies provide little evidence for a causal association between vasectomy and prostate cancer, especially given that results of studies have been inconsistent, associations when found have been mostly weak and potential for biases large, and there is no plausible biologic mechanism.¹⁹⁰ The only reported study examining vasectomy reversal to protect against prostate cancer found a non-significant reduction in prostate cancer risk in vasectomized men who had a reversal compared to vasectomized men who had not had a reversal.¹⁹¹

Studies published since the 1993 NIH expert panel  support the conclusions of that panel of experts that no change in current practice of vasectomy is warranted, that providers should continue to offer vasectomy, that vasectomy reversal is not warranted to prevent prostate cancer, and that screening for prostate cancer should not be any different in men who have had a vasectomy than in those who have not.¹⁸⁵ Based on the available evidence, the latest AUA guidance is that it is not necessary to inform men of a possible risk of prostate cancer associated with vasectomy.¹¹ While not specifically addressing prostate cancer, the current European Association of Urology guidelines recommend that prospective vasectomy clients should be told that available data indicate that vasectomy is safe and is not associated with any diseases.¹²

Table 7 summarizes results of epidemiologic studies of vasectomy and testicular cancer. With one exception,¹⁹² the studies conducted between the 1970s and early 1990s that showed an increased risk of testicular cancer following vasectomy was not statistically significant.^{93, 193, 194, 195} These studies included only small numbers of vasectomized men with testicular cancer and were subject to confounding and/or misclassification bias. Three other studies reported no increased risk,^{97, 167, 196} and Giovannucci and coworkers¹⁰³ found no cases of testicular cancer among nearly 15,000 vasectomized men. Additional studies, which included the largest numbers of cases of testicular cancer among vasectomized men, found no increased risk.^{104, 168, 197, 177} Taken together, results of these epidemiologic studies provide convincing evidence that vasectomy is not associated with an increased risk of testicular cancer.

Table 7. Summary of studies of vasectomy and testicular cancer

NR, not reported.

Information on the risk of urolithiasis in vasectomized men is available from five studies (Table 8). No significant increase in risk was reported in three of these five studies.^{17, 21, 97} Kronmal and associates,¹⁹⁸ examining data from the Coronary Artery Surgery Study registry, first reported a significantly increased risk of urolithiasis in vasectomized men in the late 1980s. Subsequently, the same investigators found a similar increased risk of urolithiasis in vasectomized men under 46 years of age, but not in those men who were 46 or over at the time of the study.¹⁹⁹ The mechanism by which vasectomy might increase the risk of urolithiasis is unclear. The public health impact of an increase in the risk of urolithiasis of the magnitude suggested in the accumulated studies to date is small.

Table 8. Summary of studies of vasectomy and urolithiasis

NR, not reported.

Chronic scrotal pain or discomfort (sometimes called postvasectomy pain syndrome) is reported by some men after vasectomy. While up to one-third to one-half of men have reported occasional scrotal discomfort after vasectomy only a small percentage of all vasectomized men (no more than 2–3%) said the pain had negatively impacted their life or that they regretted having had the vasectomy because of chronic pain.^{68, 200, 201, 202, 203} There are limited data on chronic scrotal pain in the general population and only one study of postvasectomy pain included a control group. In that study, 47% of vasectomized men reported having occasional testicular discomfort compared to 23% of controls.²⁰⁴ At nearly 4 years of follow-up, 6% of vasectomized men had pain severe enough to seek medical advice compared to 2% of the men without a vasectomy. None of the vasectomized men in the study reported that they regretted having had a vasectomy because of the pain.

The cause of chronic scrotal pain after vasectomy is poorly understood, but may be related to infection, epididymal or vas congestion, back pressure-induced epididymal tubule rupture with subsequent interstitial fibrosis, sperm granuloma formation, or nerve entrapment.^{68, 205, 206, 207, 208, 209, 210} Conservative therapy such as nonsteroidal anti-inflammatory drugs, sitz baths, antibiotics, or spermatic cord nerve blocks is sufficient treatment in most cases.^{208, 211, 210} When these fail, vasectomy reversal, epididymectomy, denervation of the spermatic cord, or excision of sperm granuloma may be helpful.^{205, 208, 211, 212, 210} Most published reports of surgical therapy for chronic scrotal pain following vasectomy involve epididymectomy^{213, 214, 215, 216, 217} or vasectomy reversal,^{205, 218, 219, 220, 221} with results suggesting that they can be effective treatments for appropriately selected individuals in cases that are not resolved with more conservative measures.  

During counselling it is important to mention that a small percentage of men experience chronic testicular pain following vasectomy. The latest AUA guidelines recommend that providers include the following statement in their preoperative counselling: “Chronic scrotal pain associated with negative impact on quality of life occurs after vasectomy in about 1–2% of men. Few of these men require additional surgery.”¹¹ 

Overall mortality rates in vasectomized and nonvasectomized men have been examined in three large cohort studies^{16, 17, 103, 105} and were found to be lower in vasectomized men in all three studies (Table 9). The most likely explanation for the lower mortality rates in vasectomized men is selection bias: that men who have had a vasectomy represent a self-selected group who may be healthier or seek health care more readily than nonvasectomized men. Authors of two of the studies suggested that the most appropriate interpretation of these data was that no evidence suggested that vasectomy leads to an overall increase in mortality rates.^{16, 103}

Table 9. Summary of studies examining total mortality in vasectomized and nonvasectomized men

* Total deaths among all men in cohort.

There have now been nearly four decades of intense research on potential long-term health effects of vasectomy. This research provides reassurance that vasectomy does not have any significant long-term negative effects and does not increase the risk of cardiovascular disease, which is the major cause of morbidity and mortality in men in developed and most developing countries.²²²  Vasectomy appears to be a safe and highly effective method of fertility control with a risk profile that compares favorably with that of methods of fertility control used by women.